Cargando…
Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α
Estrogens are suggested to play a role in the development and progression of proliferative diseases such as breast cancer. Like other steroid hormone receptors, the estrogen receptor-α (ERα) is a substrate of protein kinases, and phosphorylation has profound effects on its function and activity. Giv...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861619/ https://www.ncbi.nlm.nih.gov/pubmed/20219974 http://dx.doi.org/10.1091/mbc.E09-08-0724 |
_version_ | 1782180647794638848 |
---|---|
author | Medunjanin, Senad Weinert, Sönke Schmeisser, Alexander Mayer, Doris Braun-Dullaeus, Ruediger C. |
author_facet | Medunjanin, Senad Weinert, Sönke Schmeisser, Alexander Mayer, Doris Braun-Dullaeus, Ruediger C. |
author_sort | Medunjanin, Senad |
collection | PubMed |
description | Estrogens are suggested to play a role in the development and progression of proliferative diseases such as breast cancer. Like other steroid hormone receptors, the estrogen receptor-α (ERα) is a substrate of protein kinases, and phosphorylation has profound effects on its function and activity. Given the importance of DNA-dependent protein kinase (DNA-PK) for DNA repair, cell cycle progression, and survival, we hypothesized that it modulates ERα signaling. Here we show that, upon estrogen stimulation, DNA-PK forms a complex with ERα in a breast cancer cell line (MELN). DNA-PK phosphorylates ERα at Ser-118. Phosphorylation resulted in stabilization of ERα protein as inhibition of DNA-PK resulted in its proteasomal degradation. Activation of DNA-PK by double-strand breaks or its inhibition by siRNA technology demonstrated that estrogen-induced ERα activation and cell cycle progression is, at least, partially dependent on DNA-PK. |
format | Text |
id | pubmed-2861619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-28616192010-07-16 Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α Medunjanin, Senad Weinert, Sönke Schmeisser, Alexander Mayer, Doris Braun-Dullaeus, Ruediger C. Mol Biol Cell Articles Estrogens are suggested to play a role in the development and progression of proliferative diseases such as breast cancer. Like other steroid hormone receptors, the estrogen receptor-α (ERα) is a substrate of protein kinases, and phosphorylation has profound effects on its function and activity. Given the importance of DNA-dependent protein kinase (DNA-PK) for DNA repair, cell cycle progression, and survival, we hypothesized that it modulates ERα signaling. Here we show that, upon estrogen stimulation, DNA-PK forms a complex with ERα in a breast cancer cell line (MELN). DNA-PK phosphorylates ERα at Ser-118. Phosphorylation resulted in stabilization of ERα protein as inhibition of DNA-PK resulted in its proteasomal degradation. Activation of DNA-PK by double-strand breaks or its inhibition by siRNA technology demonstrated that estrogen-induced ERα activation and cell cycle progression is, at least, partially dependent on DNA-PK. The American Society for Cell Biology 2010-05-01 /pmc/articles/PMC2861619/ /pubmed/20219974 http://dx.doi.org/10.1091/mbc.E09-08-0724 Text en © 2010 by The American Society for Cell Biology |
spellingShingle | Articles Medunjanin, Senad Weinert, Sönke Schmeisser, Alexander Mayer, Doris Braun-Dullaeus, Ruediger C. Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α |
title | Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α |
title_full | Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α |
title_fullStr | Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α |
title_full_unstemmed | Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α |
title_short | Interaction of the Double-Strand Break Repair Kinase DNA-PK and Estrogen Receptor-α |
title_sort | interaction of the double-strand break repair kinase dna-pk and estrogen receptor-α |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861619/ https://www.ncbi.nlm.nih.gov/pubmed/20219974 http://dx.doi.org/10.1091/mbc.E09-08-0724 |
work_keys_str_mv | AT medunjaninsenad interactionofthedoublestrandbreakrepairkinasednapkandestrogenreceptora AT weinertsonke interactionofthedoublestrandbreakrepairkinasednapkandestrogenreceptora AT schmeisseralexander interactionofthedoublestrandbreakrepairkinasednapkandestrogenreceptora AT mayerdoris interactionofthedoublestrandbreakrepairkinasednapkandestrogenreceptora AT braundullaeusruedigerc interactionofthedoublestrandbreakrepairkinasednapkandestrogenreceptora |